Search Results (241)

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay. Full article

Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article

The central role of heating and cooling in energy transition has been recognised in recent years, especially with geopolitical developments since February 2022 which demand an acceleration in deploying local energy sources to increase the resilience of the energy sector. Geothermal energy is a promising and vital option to optimize heating and cooling systems, promoting sustainability of urban environments. To this end, a proper design is of paramount importance to guarantee the energy performance of the whole system. This work deals with the optimization of the technical and geometrical characteristics of borehole heat exchangers (BHEs) as part of a shallow geothermal plant that is assumed to be integrated in an already operating gas-fired DH grid. Thermal performances of three different configurations were analysed according to the geological information that revealed an aquifer at −36 m overlying a poorly permeable marly succession. Numerical simulations validated the geological, hydrogeological, and thermo-physical models by back-analysing the experimental results of a thermal response test (TRT) on a pilot 150 m deep BHE. Five-year simulations were then performed to compare 150 m and 36 m polyethylene 2U, and 36 m steel coaxial BHEs. The coaxial configuration shows the best performance both in terms of specific power (74.51 W/m) and borehole thermal resistance (0.02 mK/W). Outcomes of the study confirm that coupling the best geological and technical parameters ensure the best energy performance and economic sustainability. Full article

Background: Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible for various adverse events (AEs), in particular hepatic and dermatological AEs. Methods: To date, limited data are available in the literature regarding ocular AEs due to therapy with these drugs. In this regard, one case of corneal perforation during treatment with a VEGFR-TKI, Regorafenib, has been reported, while there are no data about Cabozantinib. In this paper, we present another clinical case of corneal perforation in a patient affected by advanced RCC and treated with Cabozantinib as a second-line therapy. The patient started Cabozantinib at the dosage of 60 mg/die although it was necessary to apply some dose reductions because of grade 2 AEs (according to CTCAE v6.0), such as asthenia, diarrhea, dysgeusia, and loss of appetite. Results: After approximately 15 months of treatment, the patient began to experience pain and vision loss in the right eye. A diagnosis of corneal perforation was made, followed by medical and surgical treatment. As regards the etiology of this pathology, all other possible causes were excluded, including a history of ocular disease, contact trauma, exposure to damaging agents (e.g., chemical agents and prolonged use of drugs such as topical NSAIDs), infections, or dry eye. Therefore, we hypothesized a correlation with Cabozantinib’s mechanisms of action and paused its administration. Conclusions: Cabozantinib may alter the ocular environment due to a lack of or imbalance in growth factors in the tear film, with a reduction in corneal epithelium proliferation. This condition might cause dry eye and a delay in corneal healing. Therefore, particular importance should be placed on ophthalmologic surveillance during treatment with these drugs in patients who develop ocular symptoms. Further in vitro and in vivo studies are necessary to deepen the knowledge about VEGFR-TKI-mediated ocular AEs. Full article

This study aims to analyze how women’s empowerment in sustainable entrepreneurial leadership transforms social, environmental, and economic challenges into growth opportunities within B Corps-certified companies in Latin America. A total of 9536 companies were identified in the global B Corps registry, of which more than 1000 belonged to the Latin America and Caribbean directory. Particular attention was given to 130 companies located in Chile, with a presence in countries such as Peru, Mexico, Colombia, Brazil, Uruguay, Paraguay, and Argentina. The methodology adopted a post-positivist approach with a hermeneutic analysis rooted in organizational studies, using the Straussian grounded theory method. Testimonies from 16 female entrepreneurs were explored, identified through the B Corps directory and the main social media networks of the B system in Latin America. This approach enabled a deeper understanding of the human complexity surrounding sustainability, equity, and gender equality. Findings show that female leadership promotes inclusive and strategic actions that challenge traditional structures and generate positive impacts. Five categories emerged: female entrepreneurial leadership; gender equality stakeholders; social contribution; women’s economic development; and sustainable decision-making. These converge in the central category of female empowerment in sustainable entrepreneurial leadership. In conclusion, the emerging theory expands the understanding of women-led leadership in Latin America, revealing socially responsible business models that promote sustainability, inclusion, and challenge dominant power structures in the business world. Full article

Purpose: This bi-centric pilot study investigates the predictive value of pre-treatment [¹⁸F]FDG PET/CT radiomics for assessing therapy response in primary mediastinal B-cell lymphoma (PMBCL). Methods: All PMBCL patients underwent PET/CT with [¹⁸F]FDG between January 2011 and January 2022 at Policlinico Tor Vergata University Hospital of Rome (70% training and 30% internal validation cohort) and Sant’Anna University Hospital of Ferrara (external validation cohort). The Deauville score (DS) was used as a predictor of therapy response (DS1-DS3 vs. DS4/DS5). A total of 121 quantitative radiomics features (RFts) were extracted from manually segmented volumes of interest (VOIs) in PET and CT images, according to IBSI. ComBat harmonization was applied to correct the center variability of features, followed by class balancing with SMOTE. Two machine learning (ML) prediction models, the PET model and the CT model, were independently developed using robust RFts. For each ML model, two different algorithms were trained (i.e., Random Forest, RF, and Support Vector Machine, SVM) using 10-fold cross validation, tested on the internal/external validation set. Receiver operating characteristic (ROC) curves, area under the curve (AUC), classification accuracy (CA), precision (Prec), sensitivity (Sen), specificity (Spec), true positive (TP) scores, and true negative (TN) scores were computed. Results: The entire dataset was composed of 29 samples for the Rome cohort (23 from D1–D3 and 6 from D4/D5) and 9 samples for the Ferrara cohort (4 from D1–D3 and 5 from D4/D5). A total of 27 RFts were identified as robust for each imaging modality. Both the CT and PET models effectively predicted the Deauville score. The performance metrics of the best classifier (SVM) for the CT and PET models in external validation were AUC = 0.75/0.80, CA = 0.85/0.77, Prec = 0.97/0.67, Sen = 0.60/0.80, Spec = 0.98/0.75, TP = 75.0%/66.7%, and TN = 77.8%/85.7%, respectively. Conclusions: ML models trained on [¹⁸F]FDG PET/CT radiomic features in PMBLC patients could predict the Deauville score. Full article

Some studies suggested a high incidence of human herpesvirus (HHV) reactivation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To evaluate the prevalence of HHV reactivations in a population with various severity degrees of coronavirus disease 2019 (COVID-19), we analyzed 102 individuals and compared them with 51 SARS-CoV-2-negative subjects admitted in the same period (January–July 2022) for acute respiratory failure. Positivity was found in 76% of subjects for at least one HHV, and in 46% for ≥2 HHV. These proportions were more prevalent in SARS-CoV-2-positive than in negative patients (83% vs. 61%; 56% vs. 27%, respectively). The most common HHV was HHV-7 both in the whole population (51%) and in SARS-CoV-2-positive and -negative subjects (57% and 39%, respectively); human cytomegalovirus, herpes simplex virus-1, Epstein–Barr virus, and HHV-6 were more represented in SARS-CoV-2-positive individuals. No single or combined HHV reactivation was associated with the 60-day mortality rate. However, cytomegalovirus reactivation was an independent predictor of COVID-19 severity and longer hospitalizations, while the occurrence of ≥3 any HHV reactivations was independently associated with the aforementioned outcomes and ventilatory support need. Taken together, our data suggest that in patients with moderate-to-severe COVID-19, the diagnosis of HHV coinfections can add useful prognostic information. Full article

Introduction: The treatment of MBC patients is guided by receptor status, with re-biopsy at relapse recommended to reassess hormone receptor (HR) status. Various treatment options are available for HER2-veMBC, including CDK4/6 inhibitors, PARP inhibitors, and checkpoint inhibitors. The study highlights the importance of determining receptor subtype for guiding treatment choices. Patients and Methods: The GIM 13 AMBRA study is a longitudinal cohort study involving 42 centers in Italy. It includes data from 939 HER2- MBC patients enrolled between May 2015 and September 2020. The study analyzes the impact of HR expression changes on clinical outcomes using Kaplan–Meier survival curves and other statistical methods. Results: Among the 939 patients, 588 were rebiopsied at first relapse. The study found no significant differences in disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS) between patients whose tumors changed molecular subtype and those who did not. However, post-progression survival from first-line treatment (PPS1) was different between the two groups. Discussion: The study confirms the phenomenon of receptor discordance between primary tumors and metastases. It emphasizes the need for re-biopsy in recurrent MBC to guide treatment strategies. The findings align with previous studies and highlight the importance of understanding receptor changes for improving patient outcomes. Conclusions: The GIM 13 AMBRA study provides valuable insights into the impact of molecular subtype changes on survival outcomes in Luminal MBC patients. It underscores the importance of re-biopsy and personalized treatment strategies in managing metastatic breast cancer. Full article

Background: Almost 30% of patients with rectal cancer (RC) who submit to comprehensive treatment experience relapse. Surveillance plays a leading role in early detection. The landmark approach provides a more flexible and dynamic framework for survival prediction. Objective: This large retrospective study aims to develop a machine learning algorithm to profile the patient prognosis, especially the risk and the onset of RC relapse after curative resection. Methods: A cohort of 2450 RC patients were analyzed using landmark analysis. Model A applied a classical cause-specific Cox approach with a landmarking approach, while Model B implemented a landmarking-based RSF (random survival forest) competing risk algorithm. The two models were compared in terms of predictive and interpretative ability. A bootstrapped validation strategy was employed to validate the model’s performance and prevent overfitting. The best-performing hyperparameters were selected systematically, ensuring the model’s robustness within the landmark approach. The study assessed these factors’ importance and interactions using RSF and compared the predictive accuracy to that of the classical Cox model. Results: Model B outperformed Model A (mean C-index 0.95 vs. 0.78), capturing complex interactions and providing dynamic, individualized relapse predictions. Clinical factors influencing survival outcomes were identified across time with the landmark approach allowing for more accurate and timely predictions. Conclusions: The landmark approach offers an improvement over traditional methods in survival analysis. By accommodating time-dependent variables and the evolving nature of patient data, this approach provides a precise tool for profiling RC survival, thereby supporting more informed and dynamic clinical decision-making. Full article

A novel instrument was designed and numerically validated for measuring AC losses in ramped superconducting magnets. These power losses are expected to be in the 1 $\mathrm{W}$ to 100 $\mathrm{W}$ range. The instrument improves metrological performance compared to existing instruments by reaching a target power loss uncertainty in the order of $0.1$ watt. This allows accurate measurement of the power losses to improve magnet modeling. A Monte Carlo analysis is used to evaluate the measurement uncertainty. Such an analysis addresses the lack of uncertainty investigation in the literature for this kind of measurement, and the proposed approach can be applied to various magnet models. The physical design of the instrument is carried out by relying on an FPGA-based acquisition platform. Results on a representative case study reveal that the target uncertainty can be reached without any compensation or correction mechanism. Instead, when aiming to use compensation or correction of the inductive magnet voltage, the sensitivity analysis points out that offset errors and time delays must be limited. This also suggests that the magnet’s inductance estimation should be improved more than the metrological performance of the instrumentation. Full article

Background/Objectives: Tibial plateau fractures (TPFs) are commonly associated with complex patterns requiring advanced surgical strategies. High-energy trauma often results in severe soft tissue damage, complicating surgical outcomes. Despite advancements in soft tissue management, postoperative complications such as surgical site infections (SSIs) remain prevalent, with rates ranging from 9.9% to 30%. This study aims to analyze risk factors and surgical approaches influencing acute SSIs following TPF fixation. Methods: A retrospective analysis was conducted on 365 patients treated for TPFs with open or arthroscopy-assisted reduction and internal fixation (ORIF/ARIF) at a single center between January 2018 and December 2023. Inclusion criteria encompassed fractures classified by the Schatzker system and definitive management through ORIF/ARIF. Exclusion criteria included non-tibial plateau fractures, polytrauma, multiligament injuries and associated femoral fractures. Patient demographics, fracture patterns, surgical interventions, and postoperative complications were reviewed. Statistical analysis was performed using chi-square and ANOVA tests, with significance set at p < 0.05. Results: The final cohort included 364 patients (mean age: 45.4 ± 17.4 years; 59.2% male). High-energy fractures (Schatzker IV–VI) accounted for 47.7%, with 6.86% being open fractures. The mean interval to surgery was 14.9 ± 20.6 days. Superficial infections occurred in 21 cases (5.8%), predominantly at external fixator pin sites, while 15 cases (4.1%) involved deep infections. A statistically significant correlation was observed between SSIs and preoperative fasciotomy (p < 0.0001), damage control orthopedic protocols (p < 0.0001), and delays in definitive treatment of 10–30 days (p < 0.0001). No significant associations were found between infection rates and fracture type, dual surgical approaches, or the use of arthroscopy. Conclusions: External fixation, preoperative fasciotomy, and delayed definitive treatment are independent risk factors for SSIs following TPF fixation. High-energy injuries and soft tissue damage exacerbate infection risk. A personalized surgical approach, based on minimally invasive techniques and optimized surgical timing may mitigate these complications and significantly improve clinical outcomes in TPFs. Full article

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence has demonstrated the role of the gut–liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment, leading to the activation of intracellular signaling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to HCC immunotherapy, respectively. The research was conducted through the analysis of Pubmed and Web of Science (WoS) databases for literature studies on the relationship between gut microbiota and HCC from 2015 to 2025. Full article

Background: Artificial iris (AI) implantation is an innovative and increasingly utilized surgical procedure for injured eyes with iris trauma. Methods: A 76-year-old female and a 34-year-old male presented at the emergency department with a traumatic corneo-scleral laceration and perforated corneal ulcer, respectively. Emergency surgeries were performed to restore ocular integrity. In both cases, a modified surgical technique involving the implantation of an AI was performed; however, two different models of AI were used. Results: The AIs were sutured with four stitches directly to the scleral-fixated (SF) intra ocular lens (IOL), and the AI-IOL complexes were implanted, as a single unit, and fixated to the sclera using the lens haptics. Before and after the surgery, patients underwent a comprehensive eye examination, including a visual acuity test. The AI-SF IOL complexes remained well positioned, with no intraocular or extraocular complications observed during the follow-up evaluations of both patients. Conclusions: We reported a straightforward and repeatable modified surgical technique for two patients with two models of AI, both sutured to the SF IOL and fixated to the sclera, as a single unit. This approach may serve as an excellent alternative for managing aphakic eyes with extensive iridodialysis or partial aniridia. Full article

Background: Hallux valgus is a common painful condition with tri-planar deformity of the first ray. Surgical correction consists of distal osteotomy of the first metatarsal and its lateral translation. However, in the case of hypermobility of the first cuneo-metatarsal joint (TMTJ), the associated Lapidus procedure is indicated to correct deformities along all three anatomical planes. Lapidus procedure is reported to have several contraindications and complications; for this reason, many surgeons proposed technical modification to the original procedure. We present the results of a novel surgical technique for hallux valgus correction with minimally invasive arthrodesis of first TMTJ without proximal correction of deformity, combined with a distal Austin-Chevron procedure. Materials and Methods: We retrospectively evaluated patients who underwent surgical correction of hallux valgus with our technique between January 2010 and January 2020. We collected data on demographics, anesthesiologic technique, associated surgical procedures, post-operative functional results, and complications. Dorso-plantar and lateral radiographs were performed at 6, 12, and 24 weeks after surgery or until fusion was documented. Clinical assessment considered gait analysis, pain or other disturbance, type of shoes worn, and use of orthosis. Results: A total of 240 patients were enrolled. AOFAS score, hallux valgus angle, and inter-metatarsal angle showed a significant improvement. Complications consisted of distal osteotomy non-union (1%), pain or protrusion of the screw (13%), and recurrence of deformity (2%). Overall, patients were very satisfied with the surgery in 192/278 (69%) cases, moderately satisfied in 67/278 (24%) cases, satisfied in 8/278 (3%) cases, and dissatisfied in 11/278 (4%) cases. Conclusions: Our novel surgical technique which combines in situ arthrodesis of the first tarso-metatarsal joint (TMTJ) with a distal Austin-Chevron procedure offers an effective alternative for correcting hallux valgus with first-ray hypermobility, minimizing complications associated with traditional methods. Full article